Reduced transplant arteriosclerosis in murine cardiac allografts placed in interferon-gamma knockout recipients.
To investigate the functional role of interferon (IFN)-gamma in transplant arteriosclerosis, BALB/c hearts were transplanted in immunosuppressed C57BL/6J recipients with (n = 10) or without (n = 10) targeted IFN-gamma gene deletion. In 55-day heart allografts, IFN-gamma deficiency resulted in a significant decrease in vascular thickening. The severity of intimal thickening measured as the percentage of luminal occlusion (mean +/- SEM) in all elastin stained vessels (n = 410) decreased from 37+/-5% in wild-type recipients to 18+/-5% in IFN-gamma -/- recipients (P < 0.005). In the few diseased vessels in grafts from IFN-gamma -/- recipients, the neointima was more cellular with a 90% increase in the nuclear density. This finding correlated with a 50% reduction in fibrosis estimated by alpha-smooth muscle actin cell accumulation in the neointima. The reduction in severity and altered composition of vascular thickening in grafts from IFN-gamma -/- recipients shows that IFN-gamma contributes to arteriosclerotic development following transplantation.
Räisänen-Sokolowski
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A
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Glysing-Jensen
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T
Koglin
J
J
Russell
M E
ME
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D016027:Heart Transplantation; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D011183:Postoperative Complications / Q000517:prevention & control*; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D007371:Interferon-gamma